Differential immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung and intestinal cells: Implications for treatment with IFN-β and IFN inducer. Issue 4 (October 2020)

• Record Type: Journal Article
• Authors: Shuai, Huiping; Chu, Hin; Hou, Yuxin; Yang, Dong; Wang, Yixin; Hu, Bingjie; Huang, Xiner; Zhang, Xi; Chai, Yue; Cai, Jian-Piao; Chan, Jasper Fuk-Woo; Yuen, Kwok-Yung
• Is Part Of: Journal of infection. Volume 81:Issue 4(2020)
• Page Start: e1
• Page End: e10
• Publication Date: 2020-10
• Subjects: SARS-CoV-2 -- COVID-19 -- Innate immune response -- IFN; Infection -- Periodicals; Bacterial Infections -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.905
• DOI: 10.1016/j.jinf.2020.07.016
• Languages: English
• ISSNs: 0163-4453

Abstract

Highlights: SARS-CoV-2 infection was more robust than SARS-CoV in Calu3. In contrast, SARS-CoV infected intestinal epithelial cells more efficiently. SARS-CoV-2 infection launched an attenuated interferon and pro-inflammatory cytokines/chemokines response in both Calu3 and Caco2 cells, despite robust virus infection and propagation. SARS-CoV-2 was more sensitive to IFNβ and poly(I:C) pretreatment than that of SARS-CoV. Summary: Objectives: Respiratory and intestinal tract are two primary target organs of SARS-CoV-2 infection. However, detailed characterization of the host-virus interplay in infected human lung and intestinal epithelial cells is lacking. Methods: We utilized immunofluorescence assays, flow cytometry, and RT-qPCR to delineate the virological features and the innate immune response of the host cells against SARS-CoV-2 infection in two prototype human cell lines representing the human lung (Calu3) and intestinal (Caco2) epithelium when compared with SARS-CoV. Results: Lung epithelial cells were significantly more susceptible to SARS-CoV-2 compared to SARS-CoV. However, SARS-CoV-2 infection induced an attenuated pro-inflammatory cytokines/chemokines induction and type I and type II IFN responses. A single dose of 10 U/mL interferon-β (IFNβ) pretreatment potently protected both Calu3 and Caco2 against SARS-CoV-2 infection. Interestingly, SARS-CoV-2 was more sensitive to the pretreatment with IFNβ and IFN inducer than SARS-CoV in Calu3. Conclusions: Despite robust infection in both human lung and intestinal epithelial cells, SARS-CoV-2 could attenuate the virus-induced pro-inflammatory response and IFN response. Pre-activation of the type I IFN signaling pathway primed a highly efficient antiviral response in the host against SARS-CoV-2 infection, which could serve as a potential therapeutic and prophylactic maneuver to COVID-19 patients.